Gloria Bonuccelli 1 , Federica Sotgia 1 , Michael P. Lisanti 1

• 1 Translational Medicine, School of Environment and Life Sciences, Biomedical Research Centre, University of Salford, Greater Manchester, United Kingdom

received: May 15, 2018 ; accepted: June 21, 2018 ; published: August 23, 2018

https://doi.org/10.18632/aging.101483
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Copyright: Bonuccelli et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Author: Anna H. Wu, Darcy Spicer, Frank Z. Stanczyk, Chiu-Chen Tseng, Chung S. Yang and Malcolm C. Pike

There have been no controlled intervention studies to investigate the effects of green tea on circulating hormone levels, an established breast cancer risk factor. We conducted a double-blind, randomized, placebo-controlled intervention study to investigate the effect of the main green tea catechin, epigallocatechin gallate (EGCG), taken in a green tea extract, polyphenon E (PPE). Postmenopausal women (n = 103) were randomized into three arms: placebo, 400-mg EGCG as PPE, or 800-mg EGCG as PPE as capsules per day for 2 months. Urinary tea catechin and serum estrogen, androgen, lipid, glucose-related markers, adiponectin, and growth factor levels were measured at baseline and at the end of months 1 and 2 of intervention. On the basis of urinary tea catechin concentrations, compliance was excellent. Supplementation with PPE did not produce consistent patterns of changes in estradiol (E2), estrone (E1), or testosterone (T) levels. Low-density lipoprotein (LDL)-cholesterol decreased significantly in both PPE groups but was unchanged in the placebo group; the change in LDL-cholesterol differed between the placebo and PPE groups (P = 0.02). Glucose and insulin levels decreased nonsignificantly in the PPE groups but increased in the placebo group; statistically significant differences in changes in glucose (P = 0.008) and insulin (P = 0.01) were found. In summary, green tea (400- and 800-mg EGCG as PPE; ∼5-10 cups) supplementation for 2 months had suggestive beneficial effects on LDL-cholesterol concentrations and glucose-related markers.

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Author: Hea Jin Park, Ji-Young Lee, Min-Yu Chung, Young-Ki Park, Allyson M. Bower, Sung I. Koo, Charles Giardina and Richard S. Bruno

Nonalcoholic steatohepatitis (NASH) is characterized by oxidative stress and inflammatory responses that exacerbate liver injury. The objective of this study was to determine whether the antioxidant and antiinflammatory activities of green tea extract (GTE) would protect against NASH in a model of diet-induced obesity. Adult Wistar rats were fed a low-fat (LF) diet or high-fat (HF) diet containing no GTE or GTE at 1% or 2% (HF+2GTE) for 8 wk. The HF group had greater (P ≤ 0.05) serum alanine (ALT) and aspartate aminotransferases and hepatic lipids than the LF group. Both GTE groups had lower ALT and hepatic lipid than the HF group. In liver and epididymal adipose, the HF group had lower glutathione as well as greater mRNA and protein expression of TNFα and monocyte chemoattractant protein-1 (MCP-1) and NFκB binding activity than the LF group. Compared to the HF group, the HF+2GTE group had greater glutathione and lower protein and mRNA levels of inflammatory cytokines in both tissues. NFκB binding activities at liver and adipose were also lower, likely by inhibiting the phosphorylation of inhibitor of NFκB. NFκB binding activities in liver and adipose (P ≤ 0.05; r = 0.62 and 0.46, respectively) were correlated with ALT, and hepatic NFκB binding activity was inversely related to liver glutathione (r = −0.35). These results suggest that GTE-mediated improvements in glutathione status are associated with the inhibition of hepatic and adipose inflammatory responses mediated by NFκB, thereby protecting against NASH.

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Author: Usha Gundimeda, Thomas H. McNeill, Albert A. Elhiani, Jason E. Schiffman, David R. Hinton and Rayudu Gopalakrishna

As the development of synthetic drugs for the prevention of stroke has proven challenging, utilization of natural products capable of preconditioning neuronal cells against ischemia-induced cell death would be a highly useful complementary approach. In this study using an oxygen-glucose deprivation and reoxygenation (OGD/R) model in PC12 cells, we show that 2-day pretreatment with green tea polyphenols (GTPP) and their active ingredient, epigallocatechin-3-gallate (EGCG), protects cells from subsequent OGD/R-induced cell death. A synergistic interaction was observed between GTPP constituents, with unfractionated GTPP more potently preconditioning cells than EGCG. GTPP-induced preconditioning required the 67-kDa laminin receptor (67LR), to which EGCG binds with high affinity. 67LR also mediated the generation of reactive oxygen species (ROS) via activation of NADPH oxidase. An exogenous ROS-generating system bypassed 67LR to induce preconditioning, suggesting that sublethal levels of ROS are indeed an important mediator in GTPP-induced preconditioning. This role for ROS was further supported by the fact that antioxidants blocked GTPP-induced preconditioning. Additionally, ROS induced an activation and translocation of protein kinase C (PKC), particularly PKCϵ from the cytosol to the membrane/mitochondria, which was also blocked by antioxidants. The crucial role of PKC in GTPP-induced preconditioning was supported by use of its specific inhibitors. Preconditioning was increased by conditional overexpression of PKCϵ and decreased by its knock-out with siRNA. Collectively, these results suggest that GTPP stimulates 67LR and thereby induces NADPH oxidase-dependent generation of ROS, which in turn induces activation of PKC, particularly prosurvival isoenzyme PKCϵ, resulting in preconditioning against cell death induced by OGD/R.

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Author: Mohammed Ehsanul Hoque Mazumder, Philip Beale, Charles Chan, Jun Q. Yu and Fazlul Huq

In this study, synergism in activity from the sequenced combinations of three trans-palladiums (denoted as TH5, TH6 and TH7) with green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG), as well as that with cisplatin, was investigated in a number of human ovarian tumour models as a function of sequence of administration. Cellular accumulation of platinum and palladium, and the levels of platinum-DNA and palladium-DNA binding were also determined for the 0/4 h and 0/0 h sequences of administration. The results of the study show that co-administration of cisplatin with EGCG (0/0 h) produces weak synergism in both cisplatin-sensitive (A2780) and cisplatin-resistant (A2780(cisR)) cell lines whereas (0/4 h) administration produces pronounced synergism in both. In contrast, bolus administration of EGCG with TH5, TH6 and TH7 produces marked antagonism except that with TH5, in the A2780(cisR) cell line, where a mild synergism is observed. In the case of TH5, TH6 and TH7, administration of drugs with a time gap (0/4 h or 4/0 h combinations) produces sequence-dependent synergism in both A2780 and A2780(cisR) cell lines, whereas in the case of cisplatin, marked antagonism is observed with the 4/0 h sequence of administration in the A2780 cell line. Whereas the highly synergistic 0/4 h sequence of combination of cisplatin with EGCG is found to be associated with pronounced cellular accumulation of platinum and a high level of platinum-DNA binding, no such clear trend can be seen for any of the combinations of TH5, TH6 and TH7 with EGCG. The results of the present study provide support to the idea that sequenced combinations of platinum drugs and tumour-active palladium compounds with selected phytochemicals such as EGCG may provide a means of overcoming drug resistance.

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Author: Christopher Masterjohn , Richard S Bruno

Nonalcoholic fatty liver disease (NAFLD) is a constellation of progressive liver disorders that are closely related to obesity, diabetes, and insulin resistance and may afflict over 70 million Americans. NAFLD may occur as relatively benign, nonprogressive liver steatosis, but in many individuals it may progress in severity to nonalcoholic steatohepatitis, fibrosis, cirrhosis, and liver failure or hepatocellular carcinoma. No validated treatments currently exist for NAFLD except for weight loss, which has a poor long-term success rate. Thus, dietary strategies that prevent the development of liver steatosis or its progression to nonalcoholic steatohepatitis are critically needed. Green tea is rich in polyphenolic catechins that have hypolipidemic, thermogenic, antioxidant, and anti-inflammatory activities that may mitigate the occurrence and progression of NAFLD. This review presents the experimental evidence demonstrating the hepatoprotective properties of green tea and its catechins and the proposed mechanisms by which these targeted dietary agents protect against NAFLD.

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Author: S. Monzen and I. Kashiwakura

Epigallocatechin-3-gallate (EGCg) is widely recognised as a powerful antioxidant and free radical scavenger. This study examined the radioprotective effects of EGCg on human granulopoiesis and erythropoiesis. Highly purified human CD34(+) haematopoietic stem/progenitor cells were prepared from human placental/umbilical cord blood. The cells were exposed to X rays at a dose rate of ∼1 Gy min(-1) and then cultured in a medium supplemented with either granulocyte colony-stimulating factor (G-CSF) or erythropoietin (EPO). EGCg (100 nM) was added to the culture immediately before or after X-irradiation. The concentration of 100-nM EGCg was determined in the authors' previous study. The number of granulocyte and erythrocyte colonies generated by X-irradiated CD34(+) cells decreased in a dose-dependent manner. Although EGCg addition yielded an ∼2-fold increase in the proliferation of each haematopoietic progenitor, no significant protective effect was observed in the surviving fraction of granulocyte progenitors (G-CSF alone: D(0)=1.06 Gy, n=1.14). However, EGCg addition before or after irradiation conferred a significantly higher protective effect on erythrocyte colony formation compared with the control (EPO alone: D(0)=0.66 Gy, n=1.56; EGCg (before): D(0)=0.43 Gy, n=5.48). EGCg addition before irradiation significantly improved the survival of erythroid progenitors subjected to radiation of <1 Gy. These results suggest that EGCg is more protective of erythropoiesis than granulopoiesis from radiation damage.

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Author: Yu Cai , Tomoko Kurita-Ochiai , Tomomi Hashizume , Masafumi Yamamoto

The purpose of this study was to determine whether epigallocatechin-3-gallate (EGCG) ameliorates Porphyromonas gingivalis -induced atherosclerosis. EGCG is a polyphenol extract from green tea with health benefits and P. gingivalis is shown here to accelerate atheroma formation in a murine model. Apolipoprotein E knockout mice were administered EGCG or vehicle in drinking water; they were then fed high-fat diets and injected with P. gingivalis three times a week for 3 weeks. Mice were then killed at 15 weeks. Atherosclerotic plaques in the proximal aorta were determined by Oil Red O staining. Atherosclerosis risk factors in serum, liver or aorta were analysed using cytokine antibody arrays, enzyme-linked immunosorbent assay and real-time PCR. Atherosclerotic lesion areas of the aortic sinus caused by P. gingivalis infection decreased in EGCG-treated groups, wherein EGCG reduced the production of C-reactive protein, monocyte chemoattractant protein-1, and oxidized low-density lipoprotein (LDL), and slightly lowered LDL/very LDL cholesterol in P. gingivalis -challenged mice serum. Furthermore, the increase in CCL2, MMP-9, ICAM-1, HSP60, CD44, LOX-1, NOX-4, p22phox and iNOS gene expression levels in the aorta of P. gingivalis -challenged mice were reduced in EGCG-treated mice. However, HO-1 mRNA levels were elevated by EGCG treatment, suggesting that EGCG, as a natural substance, inhibits P. gingivalis -induced atherosclerosis through anti-inflammatory and antioxidative effects.

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Author: Aviad Hoffman, Raymond Baxter, Abu Nasar, Thomas R. Gardner, Shantha Kumara, Carlos Cordon-Cardo, Aqeel Ahmed, Robert A. Newman, Oded Zmora, Richard L. Whelan

Introduction. Major surgery is associated with physiologic alterations that may promote tumor growth, and catechins in green tea may inhibit tumor growth. This study’s aim was to assess the impact of a green tea extract on laparotomy wound healing in mice. Methods. Mice were randomized to daily oral catechins solution (n = 25) or placebo (n = 20), underwent sham laparotomy after 10 days, and were sacrificed on postoperative day 7 or 21. The peak force and total energy required to rupture the abdominal wall wound, wound collagen content, and histology were assessed. Results. There were no wound complications in either group, and mean peak wound rupture forces and collagen concentration were similar. Mean energy was lower and more fibroblast proliferation was found in the treatment group on postoperative day 21. Conclusions. These results suggest that catechins has only mild clinically significant adverse effect on wound healing, and its perioperative use warrants further study.

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Author: T. Tounekti, E. Joubert, I. Hernández & S. Munné-Bosch

Tea, prepared from the leaves of Camellia species, has one of the highest contents of flavonoids among common food and beverage products. Tea consumption has moved beyond its pleasant flavor and cultural significance since a number of health promoting properties have been ascribed to this widespread beverage (e.g., anticancer, antiobesity and hypotensive effects). The major bioactive compounds in tea are catechins (flavan-3-ols), a group of flavonoids that include, among others, (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin-3-gallate (ECG), and (-)-epigallocatechin-3-gallate (EGCG). These compounds are also the precursors of theaflavins and thearubigins, oxidation products responsible for the taste and colour of certain tea types such as black tea. The composition of the tea leaf, and thus tea quality, is influenced by many pre-harvest factors such as the genetic make-up of the plant, region of production, horticultural and harvesting practices, and environmental conditions. Once harvested, processing, brewing, and storage conditions influence the phenolic composition and quality of tea infusions as well. In the present review we aim at outlining our current knowledge about means to increase the catechin content of teas, a cornerstone for improving the health-promoting properties of this beverage.

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